Fig. 4.
Senolytic activity of a series of rationally designed peptides in cell culture and in vivo. a-f, Line plots of the relative viability of the different peptides to dividing (black) or senescent (red) A375 cells: E1 (a), ES1 (b), ES2 (c), ES2r1 (d), ES2r2 (e) and FOXO4-DRI (f). Lines are best fit polynomial. IC50div is the concentration to kill 50% of dividing cells. IC50sen is the concentration to kill 50% of senescent cells. g, Images of mice with luciferase expressing, senescent, human melanoma cells injected orthotopically. Both ears of each mouse were injected with an equal number of doxorubicin-induced senescent A375 cells. The left ear was locally injected with ES2 (50 µL of 5 mg/mL) after imaging on day 0 and day 1 (red arrow). The right ear was injected with saline at the same time. Mice were then again imaged at day 2. h, Quantification of the fold change in radiance before and after saline or peptide treatment. Since the A375 cancer cells are senescent, there is a slight decrease in signal in the saline treated ears. ES2 (n=29), ES2r1 (n=7), ES2r2 (n=5), ES1 (n=4), and DRI (n=5) are significantly different from saline (n=38) and E1 (n=4) (ANOVA Scheffe post-hoc test). See also Fig. S3.